It has previously been shown that patients with Bartter's syndrome have an increase in sympatho-adrenal function as indicated by a significant increase in urinary norepinephrine and epinephrine excretion. Correction of the overproduction of prostaglandins by treatment with an inhibitor of prostaglandin synthesis restores urinary norepinephrine and epinephrine to normal. To test the hypothesis that potassium depletion may be the basis for the increase in prostaglandins and in sympathetic nervous system activity, hypokalemia was experimentally induced in rats. The potassium-depleted rats showed an increase in plasma norepinephrine, epinephrine and plasma renin activity. The results indicate that potassium depletion is a potent stimulus for the sympathetic nervous system and the renin-angiotensin system.